PROJECT SUMMARY/ABSTRACT Hundreds of thousands of adolescents and young adults each year sustain anterior cruciate ligament (ACL) injuries. These injuries often lead to poor knee health, including knee osteoarthritis (OA) that develops within 5- 15 years after the ACL injury when these athletes are still in young adulthood. Knee OA is a painful and debilitating condition that impacts quality of life, function, and overall health. Knee OA develops at similar rates in the tibiofemoral joint and the patellofemoral joint after ACL injury and surgery. Investigating and treating risk factors for both tibiofemoral and patellofemoral OA development is important. One risk factor for tibiofemoral OA is walking mechanics 6 months after ACL surgery, but the effect of walking gait on patellofemoral OA has not been studied early after ACL surgery. It is also unknown if walking mechanics may be improved through neuromuscular rehabilitation after surgery. The applicant?s long-term career goal is to optimize musculoskeletal and general health by investigating and developing interventions that delay or prevent the development of both primary and secondary OA and other musculoskeletal pathologies. The overall objectives of this proposal are to: 1) quantify the relationship between walking mechanics after ACL surgery and early signs of patellofemoral OA; and 2) determine the effects of post-operative neuromuscular training on walking mechanics after ACL surgery. The central hypotheses are that: 1) walking mechanics will correlate to early patellofemoral OA; and 2) walking mechanics will improve after neuromuscular training. Aim 1 will quantify the relationship between walking gait mechanics and patellofemoral (trochlear) cartilage T2 relaxation times (indicative of joint degeneration) 6 months after ACL surgery. Aim 2 will determine the effect of a specialized postoperative neuromuscular training program on the walking mechanics of athletes after ACL surgery. Walking analyses will be conducted 6 months after surgery for Aim 1 and before and after neuromuscular training as well as 1 and 2 years after surgery for Aim 2. Data will be analyzed for both aims using a validated musculoskeletal modeling approach to provide muscle and joint contact forces in addition to joint angles and moments. Quantitative magnetic resonance imaging data will also be collected 6 months after surgery for aim 1, and T2 relaxation times will be used to quantify cartilage health. The results of this project will advance rehabilitation science and clinical practice by critically evaluating the development of knee OA and rehabilitation strategies targeting a known risk factor for OA development. Findings will help improve musculoskeletal health, function, and quality of life. This proposal will also provide the applicant the foundation to conduct high quality longitudinal interventional and observational studies in rehabilitation, write compelling and impactful proposals, take research to its ultimate conclusion, publish in peer-reviewed journals, and prepare for a career as an independent clinician-scientist.